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Biomedical subjects

V Maher

Publications and source records attributed to V Maher.

6 recordsLinked to original sources

Primary prevention of coronary heart disease. What has WOSCOPS told us and what questions remain? West Of Scotland Coronary Prevention Study.

Coronary heart disease remains the major cause of death and morbidity in developed countries. As a consequence, its prevention constitutes a significant public health challenge. In recent times, our understanding of this disease process has expanded and many of the factors that influence its expression have been elucidated. In addition, a number of trials of diet and lipid-lowering drugs have been performed in an effort to tackle this problem. These studies demonstrate that when lipid levels are favourably altered, cardiovascular events are reduced without adverse effect. The rate at which event outcomes diverge between treated and untreated patients depends on the degree of atherosclerosis manifestation prior to treatment and the aggressiveness of the lipid altering strategy. Nonetheless, to date, the residual risk of cardiovascular events is still unacceptably high despite even the most potent lipid-lowering treatments used in these trials. In order to minimise the risk of future events, earlier intervention and a greater change in LDL and HDL cholesterol levels are needed in conjunction with other risk factor modifications.

Arteriosclerosis↗

Cellular cholesterol regulation--a defect in the type 2 (non-insulin-dependent) diabetic patient in poor metabolic control.

This study investigates the relationship between Type 2 (non-insulin-dependent) diabetes mellitus and hypercholesterolaemia with regard to delivery of cholesterol to cells and regulation of endogenous cholesterol synthesis. The ability of LDL, from hypercholesterolaemic and Type 2 diabetic patients, to suppress cellular cholesterologenesis and to enhance mitogen-stimulated lymphocyte proliferation was compared. Cholesterol synthesis was estimated by measuring [14C]-acetate incorporation into cholesterol and lymphocyte proliferation was assessed by [3H]-thymidine incorporation into mitogen-stimulated normal lymphocytes. The results indicate that LDL from both Type 2 diabetic patients in poor metabolic control and hypercholesterolaemic patients was significantly less effective (p less than 0.001) than LDL from non-diabetic normocholesterolaemic subjects in suppressing cholesterol synthesis in lymphocytes. LDL from all hypercholesterolaemic patients enhanced lymphocyte proliferation to a greater extent than LDL from normocholesterolaemic subjects and this effect was significantly increased using LDL from Type 2 diabetic, hypercholesterolaemic patients. Both suppression of [14C]-acetate incorporation and enhancement of [3H]-thymidine uptake could be related to an increased esterified/free cholesterol ratio in the LDL particle. The fact that cholesterol synthesis and cell proliferation were markedly altered by the above changes in LDL composition suggests a mechanism for cellular cholesterol accumulation in the Type 2 diabetic patient, even in the absence of elevated serum cholesterol levels.

Apolipoproteins B↗

Hormonal regulation of collagen synthesis in a clonal rat osteosarcoma cell line.

Collagen synthesis in rat osteosarcoma cell line 17/2 (ROS 17/2) was assessed by measuring the incorporation of [3H]proline into collagenase-digestible protein and the formation of [3H]hydroxyproline. PTH and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited collagen synthesis in ROS 17/2 cells in a time- and dose-dependent manner. PTH reduced collagen synthesis after a 3-h incubation, whereas the effect of 1,25-(OH)2D3 was somewhat slower. Maximal and half-maximal inhibition of collagen synthesis occurred at approximately 1 and 0.1 nM of each hormone, respectively. At confluency, ROS 17/2 cells synthesized 96% type I and 4% type III collagen. PTH reduced the synthesis of type I, but not type III, collagen. PTH and 1,25-(OH)2D3 also reduced procollagen mRNA levels, as determined by a dot blot hybridization assay. Thus, ROS 17/2 cells are a convenient model system for studying the hormonal regulation of collagen metabolism and gene expression in a cloned cell line with the osteoblastic phenotype.

Animals↗